Prenylated Curcumin Analogues as Multipotent Tools to Tackle Alzheimer's Disease

Federica Bisceglia, Francesca Seghetti, Massimo Serra, Morena Zusso, Silvia Gervasoni, Laura Verga, Giulio Vistoli, Cristina Lanni, Michele Catanzaro, Ersilia De Lorenzi, Federica Belluti

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Alzheimer's disease is likely to be caused by copathogenic factors including aggregation of Aβ peptides into oligomers and fibrils, neuroinflammation, and oxidative stress. To date, no effective treatments are available, and because of the multifactorial nature of the disease, it emerges the need to act on different and simultaneous fronts. Despite the multiple biological activities ascribed to curcumin as neuroprotector, its poor bioavailability and toxicity limit the success in clinical outcomes. To tackle Alzheimer's disease on these aspects, the curcumin template was suitably modified and a small set of analogues was attained. In particular, derivative 1 turned out to be less toxic than curcumin. As evidenced by capillary electrophoresis and transmission electron microscopy studies, 1 proved to inhibit the formation of large toxic Aβ oligomers, by shifting the equilibrium toward smaller nontoxic assemblies and to limit the formation of insoluble fibrils. These findings were supported by molecular docking and steered molecular dynamics simulations which confirmed the superior capacity of 1 to bind Aβ structures of different complexity. Remarkably, 1 also showed in vitro anti-inflammatory and antioxidant properties. In summary, the curcumin-based analogue 1 emerged as multipotent compound worthy to be further investigated and exploited in the Alzheimer's disease multitarget context.

Original languageEnglish
JournalACS Chemical Neuroscience
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Curcumin
Alzheimer Disease
Poisons
Oligomers
Capillary electrophoresis
Oxidative stress
Capillary Electrophoresis
Molecular Dynamics Simulation
Bioactivity
Transmission Electron Microscopy
Biological Availability
Toxicity
Molecular dynamics
Oxidative Stress
Anti-Inflammatory Agents
Agglomeration
Antioxidants
Transmission electron microscopy
Derivatives
Peptides

Keywords

  • Alzheimer's disease
  • amyloid beta oligomers and fibrils
  • capillary electrophoresis
  • curcumin analogues
  • neuroinflammation
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Cite this

Prenylated Curcumin Analogues as Multipotent Tools to Tackle Alzheimer's Disease. / Bisceglia, Federica; Seghetti, Francesca; Serra, Massimo; Zusso, Morena; Gervasoni, Silvia; Verga, Laura; Vistoli, Giulio; Lanni, Cristina; Catanzaro, Michele; De Lorenzi, Ersilia; Belluti, Federica.

In: ACS Chemical Neuroscience, 01.01.2019.

Research output: Contribution to journalArticle

Bisceglia, F, Seghetti, F, Serra, M, Zusso, M, Gervasoni, S, Verga, L, Vistoli, G, Lanni, C, Catanzaro, M, De Lorenzi, E & Belluti, F 2019, 'Prenylated Curcumin Analogues as Multipotent Tools to Tackle Alzheimer's Disease', ACS Chemical Neuroscience. https://doi.org/10.1021/acschemneuro.8b00463
Bisceglia, Federica ; Seghetti, Francesca ; Serra, Massimo ; Zusso, Morena ; Gervasoni, Silvia ; Verga, Laura ; Vistoli, Giulio ; Lanni, Cristina ; Catanzaro, Michele ; De Lorenzi, Ersilia ; Belluti, Federica. / Prenylated Curcumin Analogues as Multipotent Tools to Tackle Alzheimer's Disease. In: ACS Chemical Neuroscience. 2019.
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